Re: Is it possible to remove an enzyme inhibition?

Hello Justin,

This is a very good question that goes right to the heart of much 
biochemical research. And the answer is: it depends on the kind of 
inhibition.

You could imagine an enzyme as a big lump with very well designed pockets 
in it. As I’m sure you know, a protein is built by one or more strings of 
amino-acids that is/are folded very precisely. This is important: it 
means that if you change the way it folds ever so slightly, the enzyme 
might not work anymore, or change speed, or do something else.

Let’s say that the purpose of our enzyme is to put a phosphate onto a 
sugar. It would then have a pocket that will fit the unphosphorylated 
sugar perfectly. Very close to this pocket, it should have another pocket 
for, for instance, ATP (Adenosine triphosphate). Each binding can have an 
effect on the structure of the enzyme. Once both have bound, amino-acids 
in the protein are so placed that a phosphate will be transferred to the 
sugar, leaving a phosphorylated sugar and an ADP in the pockets. Now 
these guys don’t fit at all: they will instantly be ejected and replaced 
by new molecules. And so it goes on, as long as there is sugar and ATP.

The cell will need some control: for instance, the enzyme should slow 
down or stop what it’s doing if there is a lot of ATP in the cell. 
Typically, our enzyme would have another pocket somewhere else on its 
surface, which fits ATP. By binding in this pocket, the structure of the 
enzyme would change so that it becomes less effective or even stops 
working. The more ATP there is around, the more enzymes will be switched 
off. Or it could have one position that works as a switch: attach 
something there and the enzyme, again, shifts its structure and stops 
working.

In comes a Mad Scientist who wants to inhibit the enzyme. He might design 
a molecule that fits the pocket for the sugar, or the first pocket for 
ATP, but will not leave it: this would obviously block the reaction. Or 
he could design a molecule that would bind to the regulatory sites and 
thus switch the enzyme off. The first kind of inhibition is 
called ‘competitive’ (competes for the same binding place) and the second 
could be uncompetitive; there are variants which I will not discuss here.

From the above, I’d say chances are slim that one could modify the enzyme 
so that the competitive inhibition could be relieved as any change would 
most probably also affect the binding of the sugar that the enzyme is 
supposed to bind. However, it could be possible to block the 
uncompetitive inhibition. You would destroy the switch, which might not 
be a good idea in vivo, but there are uncompetitive inhibitors that do 
their work without actually using a physiological switch: glyphosate 
and ‘Round-up Ready’ plants come to mind. Glyphosate is an uncompetitive 
inhibitor, and plants are made insensitive to glyphosate by exchanging 
just one amino-acid in a particular enzyme.

I hope this answers your question!
Erik